Vandeputte Caroline, Kehagias Pashalina, El Housni Hakim, Ameye Lieveke, Laes Jean-François, Desmedt Christine, Sotiriou Christos, Deleporte Amélie, Puleo Francesco, Geboes Karen, Delaunoit Thierry, Demolin Gauthier, Peeters Marc, D'Hondt Lionel, Janssens Jos, Carrasco Javier, Marechal Raphaël, Galdon Maria Gomez, Heimann Pierre, Paesmans Marianne, Flamen Patrick, Hendlisz Alain
Gastro Intestinal Oncology Unit, Medical Oncology, Institut Jules Bordet, Brussels, Belgium.
Department of Medical Genetics, Hôpital Erasme-ULB, Brussels, Belgium.
Oncotarget. 2018 Apr 3;9(25):17756-17769. doi: 10.18632/oncotarget.24879.
Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.
预测性生物标志物在晚期结直肠癌（aCRC）中备受期待。对20例接受瑞戈非尼治疗的aCRC患者的肿瘤和基线血浆样本进行靶向测序，鉴定出89个肿瘤特异性突变，其中≥50%也存在于基线血浆中。优化了液滴数字PCR（ddPCR）检测方法，以监测整个治疗过程中采集的血浆样本中的循环肿瘤DNA（ctDNA）水平，并显示在监测治疗结果时使用ctDNA的绝对值而非突变体/野生型比率的重要性。高基线游离DNA（cfDNA）水平与较短的总生存期（OS）相关（风险比7.38，P=0.001）。突变拷贝数/毫升的早期增加（第14天）与显著更差的无进展生存期（PFS）（风险比6.12，P=0.008）和OS（风险比8.02，P=0.004）相关。这些数据表明早期ctDNA水平变化具有较高的预后价值，并支持将血液中的基因组标志物用作治疗工具。
